Comparative study of the actions of AP5A and alphabeta-methylene ATP on nonadrenergic noncholinergic neurogenic excitation in the guinea-pig vas deferens.

摘要

1. The agonistic and antagonistic effects of two nucleotide analogues, P1,P5-di-(adenosine-5') pentaphosphate (AP5A) and alpha,beta-methylene ATP (alpha,beta-Me ATP), have been compared in the guinea-pig isolated vas deferens. 2. In organ bath studies, both AP5A and alpha,beta-Me ATP were approximately 100 times more potent than ATP in producing phasic contractions of the vas deferens smooth muscle. Repeated additions of either agonist (1-10 microM) produced desensitization to a subsequent addition of the test substance. AP5A and alpha,beta-Me ATP were approximately equipotent in the production of desensitization. 3. After desensitization had been produced in the vas deferens by AP5A or alpha,beta-Me ATP, excitatory responses elicited by ATP (100-150 microM) and nonadrenergic field stimulation (2-20 Hz) were blocked, whereas those elicited by carbachol (1-10 microM) were augmented. 4. Intracellular electrical recordings demonstrated that AP5A and alpha,beta-Me ATP produced similar effects on membrane activity of the vas deferens. Concentration-dependent depolarizations alone were produced by both substances until the voltage threshold for action potential discharge was attained; thereafter, action potential discharges were superimposed on the depolarization and an accompanying phasic contraction was recorded. Upon restoration of the membrane potential to its control value (5-10 min after addition of either AP5A or alpha,beta-Me ATP), excitatory junction potentials (e.j.ps) elicited by field stimulation (up to 3 Hz) and spontaneous e.j.ps were reduced by AP5A (greater than 0.1 microM) in a concentration-dependent manner (as previously described for alpha,beta-Me ATP).(ABSTRACT TRUNCATED AT 250 WORDS)